VLPs in the apical ectodermal ridge (AER) cells of the limb are toxic: we observed DNA damage and apoptotic cell death ☠️ at the time of digit outgrowth, causing the limb phenotype observed in adult mice 4/
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But how do MusD VLPs in the cell drive this phenotype? 🤔 We generated 5 mutants of the MusD sequence. Our results showed that the Gag capsid is essential to drive a phenotype, but is not sufficient to generate the severe Dactylaplasia phenotype when reverse transcription is prevented. 5/
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Overall, we describe how VLP production in post-implantation embryos can interfere with organ formation 6/
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Our findings also provide a mechanism by which TE insertion uses the local regulatory landscape, restricted by 3D genome boundaries. We show insertion of the MusD in the neighboring but separated Lbx1 regulatory domain leads to expression in a different limb developmental population 7/
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This work was done in @stemundi.bsky.social lab @molgen.mpg.de, funded by @hfspo.bsky.social . THANK YOU to all authors & the amazing colleagues I was very lucky to work with❤️ We also thank the reviewers for their supportive comments & helpful suggestions, which improved a lot our manuscript! 8/
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Lastly, this work raises many new questions! Can VLPs cause other developmental pathologies? Why are certain developmental cells more vulnerable to VLPs than others? More generally, how do TE insertions contribute to pathological and healthy developmental phenotypes? 👇👇 9/
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My newly established lab @mpi-ie.bsky.social will investigate these questions & everything related to TEs in mammalian development. Please get in touch if you are interested! 10/10
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